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DNA methylation
About DNA methylation is process of genetic regulation that involves the addition of a methyl group (CH3) to cytosine paired with guanine (CpG) in nucleotide sequences. This modifications alters the ability of cell's to express specific genes within their genome, and is usually a permanent change that is maintained as cells divide. This process is vitally important for healthy growth and development in humans, and is linked to various processes such as genomic imprinting and carcinogenesis with the suppression of repetitive elements. DNA methylation causes the expression of retrioviral genes to be suppressed as well as potentially mutated or dangerous sequences of DNA that have entered and may damage the host. On the other hand, aberrant methylation patterns have shown to play a role in the development of cancer as a key regulator in gene expression. High rates of malignancy have been shown to exist in association with these patterns. It has also been shown that genes with a high concentration of 5-methylcytosine are transcriptionally silent, which can prevent the sequencing of specific amino acids during protein formation, leading to dysfunction proteins. Altogether, methylation of specific segments of DNA directly affects the ability of the cells to express various genes, and it's regulation is tightly controlled through specific mechanisms. Mechanisms of Regulation DNA methylation occurs most exclusively on a cytosine in a CpG nucleotide, is achieved by the addition of a methyl group to the 5 position of a cytosine ring. This addition is mediated by the enzyme DNA methyltransferase (DNMTs). CpG sites are about 80% depleted in the genome and are asymmetrically distributed in dense regions called CpG islands. The regions normally remain unmethylated, however methylation of CpG islands in promoter regions is associated with gene silencing. The methylation of certain DNA sequences interrupts the interaction of general transcription factors with the sequence of DNA. This prevention of binding is what inhits transcription for occurring. Recent studies have shown that micro-RNAs (miRNA) are also associated with methylation. miRNAs are a class of small non-coding RNA molecules that regulate eukaryotic gene expression at the post transcriptional level. They are able to specifically bind in their 3 prime untranslated regions (UTRs) based on specific sequences, and therefore lead to translational repression and gene silencing. miRNAs bind to their mRNAs and down regulate their stability and translation, and can also bind to targets with incomplete complementarity, often in the 3′-UTR regions, which ultimately leads to translational suppression.The vast quantity of miRNA's discovered suggests that many biological processes such as control of the cell cycle, and apoptosis and embryo development. Each miRNA has also been predicted to have many targets, and each mRNA may be able to recognize and bind more than one mRNA. The combination of both these regulation methods results in complete suppression of targeted genes. Factors affecting regulation Although many environmental factors affect DNA methylation, stress perhaps has the greatest impact. A study was preformed on shift work nurses, which are consistently under a great deal of stress. Increased stress levels puts individuals at an increase for burnout and depression. The affects of stress on the serotonin transporter gene (SLC6A4) promoter methylation were examined using bisulfite sequencing. Nurses were exposed to high and low stress environments, and five CpG residues of a CpG rich region in the SLC6A4 promoter was measured for extent of methylation. The DNA from the subjects was isolated and examined from peripheral leukocytes. It was found the nurses in the high stress environments had particularly lower promoter methylation levels of all five CpGs compared to nurses in low stress environments. Burnout and work stress levels were significant contributors and could be correlated to methylation levels. The lower methylation of the SLC6A4 promoter in high stress conditions suggests an increase in transcription of the gene, and therefore an increased re-uptake of serotonin from synaptic clefts. Scientists predict that this phenomena is associated with a possible coping mechanism for environmental stress in humans. This also explains why individuals sometimes experience an increase in depression in long-term stressful situations. A short-term increase in serotonin can help he body cope, however long-term decreased methylation will act to deplete the body's serotonin reserves and will untimatly impact the individual in a negative way. Resources [http://www.nature.com/srep/2014/141013/srep06546/full/srep06546.html 1. Huang, Young-Zhen. "Genome-wide DNA Methylation Profiles and Their Relationships with MRNA and the MicroRNA Transcriptome in Bovine Muscle Tissue (Bos Taurine)." Nature.com. Nature Publishing Group, n.d. Web. 19 Oct. 2014.] [http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0045813 2. Alasaari, Jukka S. "Environmental Stress Affects DNA Methylation of a CpG Rich Promoter Region of Serotonin Transporter Gene in a Nurse Cohort." PLOS ONE:. PLOS 1, n.d. Web. 19 Oct. 2014.] [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161384/ 3. Ricceri, Fulvio, Morena Trevisan, Valentina Fiano, Chiara Grasso, Francesca Fasanelli, Chiara Scoccianti, Laura De Marco, Anna Gillio Tos, Paolo Vineis, and Carlotta Sacerdote. "Abstract." National Center for Biotechnology Information. U.S. National L]ibrary of Medicine, 11 Sept. 2014. Web. 19 Oct. 2014. [[wikipedia:DNA_methylation|4. "DNA Methylation." Wikipedia. Wikimedia Foundation, 19 Oct. 2014. Web. ]] [http://www.news-medical.net/health/DNA-Methylation-What-is-DNA-Methylation.aspx 5. Mandal, Dr Ananya. "What Is DNA Methylation?" News-Medical.net. N.p., n.d. Web. 19 Oct. 2014.]